Lymphatic filariasis (LF), caused primarily by Wuchereria bancrofti, and malaria, caused primarily by Plasmodium falciparum and P. vivax, are two of the most important mosquito-borne diseases. They cause mortality and morbidity in hundreds of millions of people living in the tropical and subtropical regions of the world and place over two billion more at risk. The economic and health impacts these diseases place on populations have undoubtedly been driving forces in the recent development of global strategies for their control and/or elimination. These control programs need to define and quantify epidemiologically valid endpoints for meeting program objectives, but to do this it is necessary to obtain a critical understanding of transmission dynamics operating between vectors and human hosts. Understanding the relationship a parasite has with its mosquito vector, i.e., vector competence, is critical to this effort. Vector competence of mosquitoes to LF or Plasmodium parasites is affected by the innate immune response of mosquito vectors, but the impact of vector immune responses on transmission of these parasites in endemic areas has seldom been evaluated. During the last year, we conducted preliminary studies in Papua New Guinea (PNG) that demonstrate that Anopheles punctulatus, a principal vector of W. bancrofti, mounts a strong melanization immune response against this parasite. As a result of these findings, we propose the overall hypothesis that melanization immune responses by anopheline vectors significantly impact transmission of W. bancrofti in PNG. Because LF and malaria are co-endemic in PNG, and because the An. punctulatus complex of species transmits both LF parasites and all endemic species of Plasmodium, we also propose the hypothesis that immune response activation by W. bancrofti negatively impacts the development of P. falciparum when mosquitoes are exposed to both parasites. To test these hypotheses we herein propose collaboration with the PNG Institute of Medical Research (PNGIMR) that will (1) determine the impact of melanization immune responses on the development of W. bancrofti in anopheline mosquitoes in PNG, and (2) evaluate the impact of mosquito anti-filarial worm responses on the development of P. falciparum. This research will be done primarily in PNG at the PNGIMR in collaboration with Peter Siba, as an extension of NIH Grant No. RO1AI19769, 04/01/1983 to 02/29/2012. PUBLIC HEALTH RELEVANCE: Malaria and lymphatic filariasis are mosquito-borne diseases that exact a devastating toll on human health, especially amongst less privileged populations in the tropics. The research described in this proposal will give the scientific community a better understanding of mosquito-parasite interrelationships that can influence the efficiency of disease transmission by these vectors. This increased understanding of factors influencing transmission dynamics will provide valuable information for the design and monitoring of control and/or elimination programs.